Aging Aggravates Cachexia in Tumor-Bearing Mice

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorGEPPERT, Julia
dc.contributor.authorWALTH, Alina A.
dc.contributor.authorEXPOSITO, Raul Terron
dc.contributor.authorKALTENECKER, Doris
dc.contributor.authorMORIGNY, Pauline
dc.contributor.authorMACHADO, Juliano
dc.contributor.authorBECKER, Maike
dc.contributor.authorSIMOES, Estefania
dc.contributor.authorLIMA, Joanna D. C. C.
dc.contributor.authorDANIEL, Carolin
dc.contributor.authorDIAZ, Mauricio Berriel
dc.contributor.authorHERZIG, Stephan
dc.contributor.authorSEELAENDER, Marilia
dc.contributor.authorROHM, Maria
dc.date.accessioned2022-04-19T12:54:24Z
dc.date.available2022-04-19T12:54:24Z
dc.date.issued2022
dc.description.abstractSimple Summary Cachexia is a deadly disease that accompanies many different types of cancers. Animal studies on cachexia have so far mostly been conducted using young mice, while cancer in humans is a disease of high age. Mouse models used to date may therefore not be suitable to study cachexia with relevance to patients. By comparing young and old mice of three different strains and two different tumor types, we here show that the age of mice has a substantial effect on cachexia progression (specifically body weight, tissue weight, fiber size, molecular markers) that is dependent on the mouse strain studied. This is independent of glucose tolerance. The cachexia markers IL6 and GDF15 differ between ages in both mice and patients. Future studies on cachexia should consider the age and strain of mice. Background: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer. Results: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients. Conclusions: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.eng
dc.description.indexPubMedeng
dc.identifier.citationCANCERS, v.14, n.1, article ID 90, 21p, 2022
dc.identifier.doi10.3390/cancers14010090
dc.identifier.eissn2072-6694
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/45790
dc.language.isoeng
dc.publisherMDPIeng
dc.relation.ispartofCancers
dc.rightsopenAccesseng
dc.rights.holderCopyright MDPIeng
dc.subjectagingeng
dc.subjectcachexiaeng
dc.subjectcancereng
dc.subjectmouse modelseng
dc.subject.othercancer cachexiaeng
dc.subject.otherskeletal-muscleeng
dc.subject.otherexpressioneng
dc.subject.otheradenocarcinomaeng
dc.subject.otherageeng
dc.subject.wosOncologyeng
dc.titleAging Aggravates Cachexia in Tumor-Bearing Miceeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryAlemanha
hcfmusp.affiliation.countryisode
hcfmusp.author.externalGEPPERT, Julia:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalWALTH, Alina A.:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalEXPOSITO, Raul Terron:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalKALTENECKER, Doris:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalMORIGNY, Pauline:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalMACHADO, Juliano:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalBECKER, Maike:German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany; Helmholtz Ctr Munich, Res Grp Immune Tolerance Diabet, Helmholtz Diabet Ctr, Inst Diabet Res, D-85764 Neuherberg, Germany
hcfmusp.author.externalLIMA, Joanna D. C. C.:Univ Sao Paulo, Dept Surg, Fac Med, BR-01246903 Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, LIM 26, BR-01246903 Sao Paulo, Brazil
hcfmusp.author.externalDANIEL, Carolin:German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany; Helmholtz Ctr Munich, Res Grp Immune Tolerance Diabet, Helmholtz Diabet Ctr, Inst Diabet Res, D-85764 Neuherberg, Germany; Ludwig Maximilians Univ Munchen, Div Clin Pharmacol, Dept Med 4, D-80539 Munich, Germany
hcfmusp.author.externalDIAZ, Mauricio Berriel:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.author.externalHERZIG, Stephan:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany; Tech Univ Munich, TUM Sch Med, Chair Mol Metab Control, Fac Med, D-80333 Munich, Germany
hcfmusp.author.externalROHM, Maria:Helmholtz Ctr Munich, Inst Diabet & Canc, D-85764 Neuherberg, Germany; Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Inner Med 1, D-69120 Heidelberg, Germany; German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany
hcfmusp.citation.scopus9
hcfmusp.contributor.author-fmusphcESTEFANIA SIMOES FERNANDEZ
hcfmusp.contributor.author-fmusphcMARILIA CERQUEIRA LEITE SEELAENDER
hcfmusp.description.articlenumber90
hcfmusp.description.issue1
hcfmusp.description.volume14
hcfmusp.origemWOS
hcfmusp.origem.pubmed35008253
hcfmusp.origem.scopus2-s2.0-85121612552
hcfmusp.origem.wosWOS:000758527800001
hcfmusp.publisher.cityBASELeng
hcfmusp.publisher.countrySWITZERLANDeng
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